HIV is a sexually transmitted disease, and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. The purpose of this project is to use the SIV/rhesus macaque system to define the best immunization strategy to elicit genital mucosal immune responses. Using an immunization protocol developed by Dr. Lehner that specifically directs antigen to the genital lymph nodes; 3 female rhesus macaques were immunized with whole inactivated SIV in alum and 3 animals were immunized with SIVgp120 and SIVp27 in alum. The patterns of antigen specific cytokine secretion in CD4+ T cells was analyzed in the laboratory of Dr. Kiyono, and all animals had Th1-like patterns of cytokine secretion after 1 inoculation. The pattern of cytokine secretion became Th2-like in 5 of 6 animals but remained Th1-like in 1 animal after boosting. The animals were challenged 14 days after the 2nd boost by intravaginal SIV inoculation. Four of 4 naive control animals became infected and 5 of 6 vaccinated animals became infected. The one immunized animal in which infectious virus could not be detected maintained a Th1-like pattern of cytokine secretion throughout the immunization protocol. Three more animals were similarly immunized with SIVp55 and gp140. The animals made good immune responses but were not protected from vaginal challenge with SIV. *KEY*Targeted lymph node vaccines, T helper cell subsets